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https://www.readbyqxmd.com/read/28213589/sh479-a-betulinic-acid-derivative-ameliorates-experimental-autoimmune-encephalomyelitis-by-regulating-the-th17-treg-balance
#1
Jing Li, Ji Jing, Yang Bai, Zhen Li, Roumei Xing, Binhe Tan, Xueyun Ma, Wenwei Qiu, Changsheng Du, Bing Du, Fan Yang, Jie Tang, Stefan Siwko, Mingyao Liu, Huaqing Chen, Jian Luo
CD4+ T helper cells, especially Th17 cells, combined with immune regulatory network dysfunction, play key roles in autoimmune diseases including multiple sclerosis (MS). Betulinic acid (BA), a natural pentacyclic triterpenoid, has been reported to be involved in anti-inflammation, in particular having an inhibitory effect on pro-inflammatory cytokine IL-17 and IFN-γ production. In this study, we screened BA derivatives and found a BA derivative, SH479, which had a greater inhibitory effect on Th17 differentiation...
February 17, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28209777/cd6-as-a-potential-target-for-treating-multiple-sclerosis
#2
Yan Li, Nora G Singer, Joy Whitbred, Michael A Bowen, David A Fox, Feng Lin
CD6 was established as a marker of T cells more than three decades ago, and recent studies have identified CD6 as a risk gene for multiple sclerosis (MS), a disease in which autoreactive T cells are integrally involved. Nevertheless, the precise role of CD6 in regulating T-cell responses is controversial and its significance in the pathogenesis of various diseases remains elusive, partly due to the lack of animals engineered to alter expression of the CD6 gene. In this report, we found that CD6 KO mice showed decreased pathogenic T-cell responses, reduced spinal cord T-cell infiltration, and attenuated disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
February 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28209331/treatment-effectiveness-of-alemtuzumab-compared-with-natalizumab-fingolimod-and-interferon-beta-in-relapsing-remitting-multiple-sclerosis-a-cohort-study
#3
Tomas Kalincik, J William L Brown, Neil Robertson, Mark Willis, Neil Scolding, Claire M Rice, Alastair Wilkins, Owen Pearson, Tjalf Ziemssen, Michael Hutchinson, Christopher McGuigan, Vilija Jokubaitis, Tim Spelman, Dana Horakova, Eva Havrdova, Maria Trojano, Guillermo Izquierdo, Alessandra Lugaresi, Alexandre Prat, Marc Girard, Pierre Duquette, Pierre Grammond, Raed Alroughani, Eugenio Pucci, Patrizia Sola, Raymond Hupperts, Jeannette Lechner-Scott, Murat Terzi, Vincent Van Pesch, Csilla Rozsa, François Grand'Maison, Cavit Boz, Franco Granella, Mark Slee, Daniele Spitaleri, Javier Olascoaga, Roberto Bergamaschi, Freek Verheul, Steve Vucic, Pamela McCombe, Suzanne Hodgkinson, Jose Luis Sanchez-Menoyo, Radek Ampapa, Magdolna Simo, Tunde Csepany, Cristina Ramo, Edgardo Cristiano, Michael Barnett, Helmut Butzkueven, Alasdair Coles
BACKGROUND: Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years. METHODS: In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts...
February 10, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28203460/the-prevalence-of-anti-aquaporin-4-antibody-in-patients-with-idiopathic-inflammatory-demyelinating-diseases-presented-to-a-tertiary-hospital-in-malaysia-presentation-and-prognosis
#4
S Abdullah, W F Wong, C T Tan
Background. There have been inconsistent reports on the prevalence and pathogenicity of anti-Aquaporin 4 (AQP4) in patients presented with idiopathic inflammatory demyelinating diseases (IIDDs). Objective. To estimate the prevalence of anti-AQP4 antibody in patients with IIDDs presented to University Malaya Medical Centre in terms of patients' clinical and radiological presentations and prognoses. Methods. Retrospective data review of IIDDs patients presented from 2005 to 2015. Patients were classified into classical multiple sclerosis (CMS), opticospinal (OS) presentation, optic neuritis (ON), transverse myelitis (TM), brainstem syndrome (BS), and tumefactive MS...
2017: Multiple Sclerosis International
https://www.readbyqxmd.com/read/28199381/impact-of-the-anti-aquaporin-4-autoantibody-on-inner-retinal-structure-function-and-structure-function-associations-in-japanese-patients-with-optic-neuritis
#5
Yoshiko Matsumoto, Sotaro Mori, Kaori Ueda, Takuji Kurimoto, Akiyasu Kanamori, Yuko Yamada, Ichiro Nakashima, Makoto Nakamura
PURPOSE: An autoantibody against aquaporin-4 (AQP4 Ab) is highly specific for neuromyelitis optica spectrum disorder and plays a pathogenic role in this disease. The purpose of this study was to investigate the impact of AQP4 Ab on inner retinal structure, function, and the structure-function relationships in eyes with optic neuritis. METHODS: Thirty five eyes from 25 cases who had received visual function tests and RTVue optical coherence tomography (OCT) measurement at least six months after the latest episode of optic neuritis were enrolled...
2017: PloS One
https://www.readbyqxmd.com/read/28197337/defective-t-cell-control-of-epstein-barr-virus-infection-in-multiple-sclerosis
#6
Michael P Pender, Peter A Csurhes, Jacqueline M Burrows, Scott R Burrows
Mounting evidence indicates that infection with Epstein-Barr virus (EBV) has a major role in the pathogenesis of multiple sclerosis (MS). Defective elimination of EBV-infected B cells by CD8(+) T cells might cause MS by allowing EBV-infected autoreactive B cells to accumulate in the brain. Here we undertake a comprehensive analysis of the T-cell response to EBV in MS, using flow cytometry and intracellular IFN-γ staining to measure T-cell responses to EBV-infected autologous lymphoblastoid cell lines and pools of human leukocyte antigen (HLA)-class-I-restricted peptides from EBV lytic or latent proteins and cytomegalovirus (CMV), in 95 patients and 56 EBV-seropositive healthy subjects...
January 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28193696/astrocytic-orosomucoid-2-modulates-microglial-activation-and-neuroinflammation
#7
Myungjin Jo, Jong-Heon Kim, Gyunjee Song, Minchul Seo, Eun Mi Hwang, Kyoungho Suk
Orosomucoid (ORM) is an acute-phase protein that belongs to the immunocalin subfamily, a group of small-molecule binding proteins with immunomodulatory functions. Little is known about the role of ORM proteins in the central nervous system. The aim of the present study was to investigate the brain expression of ORM and its role in neuroinflammation. Expression of Orm2, but not Orm1 or Orm3, was highly induced in the mouse brain after systemic injection of lipopolysaccharide (LPS). Plasma levels of ORM2 were also significantly higher in patients with cognitive impairment than in normal subjects...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28193690/lingo-1-regulates-oligodendrocyte-differentiation-through-the-cytoplasmic-gelsolin-signaling-pathway
#8
Zhaohui Shao, Xinhua Lee, Guanrong Huang, Guoqing Sheng, Christopher E Henderson, Daniel Louvard, Jiho Sohn, Blake Pepinsky, Sha Mi
Differentiation and maturation of oligodendrocyte progenitor cells (OPCs) involve the assembly and disassembly of actin microfilaments. How actin dynamics is regulated during this process remains poorly understood. Leucine rich repeat and Immunoglobulin-like domain-containing Nogo receptor interacting protein 1(LINGO-1) is a negative regulator of OPC differentiation. We discovered that anti-LINGO-1 antibody promoted OPC differentiation was accompanied by upregulation of cytoplasmic gelsolin (cGSN), an abundant actin-severing protein involved in the depolymerization of actin filaments...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28180112/oral-multiple-sclerosis-drugs-inhibit-the-in-vitro-growth-of-epsilon-toxin-producing-gut-bacterium-clostridium-perfringens
#9
Kareem R Rumah, Timothy K Vartanian, Vincent A Fischetti
There are currently three oral medications approved for the treatment of multiple sclerosis (MS). Two of these medications, Fingolimod, and Teriflunomide, are considered to be anti-inflammatory agents, while dimethyl fumarate (DMF) is thought to trigger a robust antioxidant response, protecting vulnerable cells during an MS attack. We previously proposed that epsilon toxin from the gut bacterium, Clostridium perfringens, may initiate newly forming MS lesions due to its tropism for blood-brain barrier (BBB) vasculature and central nervous system myelin...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28174515/upregulation-of-bcl-2-and-its-promoter-signals-in-cd4-t-cells-during-neuromyelitis-optica-remission
#10
Tao Yang, Su Wang, Xiao Yang, Qi Zheng, Lei Wang, Qian Li, Mingyan Wei, Zongpan Du, Yongping Fan
The homeostatic balance between production and elimination of CD4+ T cells in peripheral blood plays an important role in patients with neuromyelitis optica (NMO). The objective of the present study was to evaluate the anti-apoptosis genes Bcl-2 and its promoter signal (nuclear factor kappa-light-chain-enhancer of activated B cells, NFκB) in CD4+ T cells. Healthy subjects (HS, n = 25) and patients with multiple sclerosis (MS) (n = 25) and NMO (n = 30) in remission were consecutively enrolled in this prospective study between May and December 2015...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28170401/clinical-practice-of-analysis-of-anti-drug-antibodies-against-interferon-beta-and-natalizumab-in-multiple-sclerosis-patients-in-europe-a-descriptive-study-of-test-results
#11
Jenny Link, Ryan Ramanujam, Michael Auer, Malin Ryner, Signe Hässler, Delphine Bachelet, Cyprien Mbogning, Clemens Warnke, Dorothea Buck, Poul Erik Hyldgaard Jensen, Claudia Sievers, Kathleen Ingenhoven, Nicolas Fissolo, Raija Lindberg, Verena Grummel, Naoimh Donnellan, Manuel Comabella, Xavier Montalban, Bernd Kieseier, Per Soelberg Sørensen, Hans-Peter Hartung, Tobias Derfuss, Andy Lawton, Dan Sikkema, Marc Pallardy, Bernhard Hemmer, Florian Deisenhammer, Philippe Broët, Pierre Dönnes, Julie Davidson, Anna Fogdell-Hahn
Antibodies against biopharmaceuticals (anti-drug antibodies, ADA) have been a well-integrated part of the clinical care of multiple sclerosis (MS) in several European countries. ADA data generated in Europe during the more than 10 years of ADA monitoring in MS patients treated with interferon beta (IFNβ) and natalizumab have been pooled and characterized through collaboration within a European consortium. The aim of this study was to report on the clinical practice of ADA testing in Europe, considering the number of ADA tests performed and type of ADA assays used, and to determine the frequency of ADA testing against the different drug preparations in different countries...
2017: PloS One
https://www.readbyqxmd.com/read/28165507/paeoniflorin-ameliorates-experimental-autoimmune-encephalomyelitis-via-inhibition-of-dendritic-cell-function-and-th17-cell-differentiation
#12
Han Zhang, Yuanyuan Qi, Yuanyang Yuan, Li Cai, Haiyan Xu, Lili Zhang, Bing Su, Hong Nie
Paeoniflorin (PF) is a monoterpene glycoside and exhibits multiple effects, including anti-inflammation and immunoregulation. To date, the effect of PF on multiple sclerosis (MS) has not been investigated. In this study, we investigated the effect of PF in experimental autoimmune encephalomyelitis (EAE), an animal model for MS. After administered with PF, the onset and clinical symptoms of EAE mice were significantly ameliorated, and the number of Th17 cells infiltrated in central nervous system (CNS) and spleen was also dramatically decreased...
February 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28165135/multiple-sclerosis-associated-retrovirus-epstein-barr-virus-and-vitamin-d-status-in-patients-with-relapsing-remitting-multiple-sclerosis
#13
Aliehossadat Mostafa, Somayeh Jalilvand, Zabihollah Shoja, Ahmad Nejati, Shohreh Shahmahmoodi, Mohammad Ali Sahraian, Sayed Mahdi Marashi
The relationship between infections and autoimmune diseases is complex and there are several reports highlighting the role of human endogenous retroviruses (HERVs) in these patients. The levels of multiple sclerosis-associated retrovirus (MSRV)-type DNA of Env gene was measured in peripheral blood mononuclear cells from 52 patients with relapsing-remitting multiple sclerosis (RRMS) and 40 healthy controls using specific quantitative PCR (qPCR) analysis. Furthermore, we analyzed the status of HERV-W/MSRV in these patients with regards to both EBV (DNA load and anti-EBNA1 IgG antibody) and vitamin D concentration...
February 6, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28160128/blockade-of-the-kinin-b1-receptor-affects-the-cytokine-chemokine-profile-in-rat-brain-subjected-to-autoimmune-encephalomyelitis
#14
Karolina Podsiadło, Grzegorz Sulkowski, Beata Dąbrowska-Bouta, Lidia Strużyńska
Kinins are bioactive peptides which provide multiple functions, including critical regulation of the inflammatory response. Released during tissue injury, kinins potentiate the inflammation which represents a hallmark of numerous neurological disorders, including those of autoimmune origin such as multiple sclerosis (MS). In the present work, we assess the expression of B1 receptor (B1R) in rat brain during the course of experimental autoimmune encephalomyelitis (EAE) which is an animal model of MS. We apply pharmacological inhibition to investigate the role of this receptor in the development of neurological deficits and in shaping the cytokine/chemokine profile during the course of the disease...
February 3, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28158203/silymarin-suppresses-basal-and-stimulus-induced-activation-exhaustion-differentiation-and-inflammatory-markers-in-primary-human-immune-cells
#15
Erica S Lovelace, Nicholas J Maurice, Hannah W Miller, Chloe K Slichter, Robert Harrington, Amalia Magaret, Martin Prlic, Stephen De Rosa, Stephen J Polyak
Silymarin (SM), and its flavonolignan components, alter cellular metabolism and inhibit inflammatory status in human liver and T cell lines. In this study, we hypothesized that SM suppresses both acute and chronic immune activation (CIA), including in the context of HIV infection. SM treatment suppressed the expression of T cell activation and exhaustion markers on CD4+ and CD8+ T cells from chronically-infected, HIV-positive subjects. SM also showed a trend towards modifying CD4+ T cell memory subsets from HIV+ subjects...
2017: PloS One
https://www.readbyqxmd.com/read/28145788/preclinical-and-pharmacotoxicology-evaluation-of-%C3%AE-l-guluronic-acid-g2013-as-a-non-steroidal-anti-inflammatory-drug-with-immunomodulatory-property
#16
Sepideh Nazeri, Shahin Khadem Azarian, Mohammad Javad Fattahi, Reza Sedaghat, Farzaneh Tofighi Zavareh, Zahra Aghazadeh, Mohammad Abdollahi, Abbas Mirshafiey
CONTEXT: Therapeutic effects of α-l-guluronic acid with the greatest tolerability and efficacy (G2013) have been shown in experimental model of multiple sclerosis and other in vitro and in vivo examinations regarding α-l-guluronic acid; there are no toxicological researches on its safety although the pharmacological impacts have been recorded. OBJECTIVE: This study was designed to determine the acute and sub chronic toxicity of α-l-guluronic acid in healthy male and female BALB/c mice...
February 1, 2017: Immunopharmacology and Immunotoxicology
https://www.readbyqxmd.com/read/28139754/intranasal-delivery-of-a-novel-amnion-cell-secretome-prevents-neuronal-damage-and-preserves-function-in-a-mouse-multiple-sclerosis-model
#17
Reas S Khan, Kimberly Dine, Bailey Bauman, Michael Lorentsen, Lisa Lin, Helayna Brown, Leah R Hanson, Aleta L Svitak, Howard Wessel, Larry Brown, Kenneth S Shindler
The ability of a novel intranasally delivered amnion cell derived biologic to suppress inflammation, prevent neuronal damage and preserve neurologic function in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis was assessed. Currently, there are no existing optic nerve treatment methods for disease or trauma that result in permanent vision loss. Demyelinating optic nerve inflammation, termed optic neuritis, induces permanent visual dysfunction due to retinal ganglion cell damage in multiple sclerosis and experimental autoimmune encephalomyelitis...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28137763/monocyte-siglec-14-expression-is-upregulated-in-patients-with-systemic-lupus-erythematosus-and-correlates-with-lupus-disease-activity
#18
Susannah I Thornhill, Anselm Mak, Bernett Lee, Hui Yin Lee, Michael Poidinger, John E Connolly, Anna-Marie Fairhurst
OBJECTIVE: Siglecs are sialic acid-binding immunoglobulin-like lectins expressed on the surface of immune cells, which participate in the discrimination of self and non-self. We investigated myeloid CD33-related Siglec expression in a cohort of patients with SLE. METHODS: Cell surface expression of Siglec-5/14, Siglec-9 and Siglec-10 on peripheral myeloid subsets were analysed from 39 SLE patients using flow cytometry. Genotyping of the Siglec-5/14 locus was also performed...
January 29, 2017: Rheumatology
https://www.readbyqxmd.com/read/28137608/silymarin-protects-against-acrylamide-induced-neurotoxicity-via-nrf2-signalling-in-pc12-cells
#19
Liang Li, Hong-Yang Sun, Wei Liu, Hong-Yu Zhao, Mei-Li Shao
Silymarin (SM) is a well-known antioxidant, anti-inflammatory and anti-cancer compound extracted from the milk thistle. Here, we investigated the protective effect of SM against acrylamide (AA)-induced neurotoxicity, mainly caused by oxidative stress, via activation of the nuclear transcription factor E2-related factor 2 (Nrf2) signalling pathway in PC12 cells. The MTT reduction assay was used to measure cell viability in various drug-treated groups and demonstrated that SM could increase cell viability in AA-treated PC12 cells...
January 27, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28134563/zenit-ra-evaluation-a-solid-phase-chemiluminescence-immunoassay-for-detection-of-anti-cellular-antibodies
#20
Enrique Melguizo Madrid, Concepción González-Rodríguez, María de Gracia Ávila-García, Teresa Arrobas-Velilla, Patricia Fernández-Riejos
AIM: The objective was to compare Zenit RA chemiluminescent immunoassay (CLIA) from Menarini Diagnostics and ELISA from INOVA Diagnostics for the presence of specific anti-Ro/SS-A, anti-La/SS-B, anti-U1snRNP, anti-Sm, anti-Scl-70, anti-Jo-1 antibodies. Results/methodology: We studied 501 samples (178 connective autoimmune disease, 150 other autoimmune or inflammatory disease and 173 other disease or healthy). All samples were analyzed using CLIA and ELISA. The Kappa agreement was excellent for anti-SSA/Ro (0...
January 30, 2017: Bioanalysis
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